The long-term objective of this study is to evaluate the relationships between hormone replacement therapy (HRT) and breast cancer detection, breast cancer risk, breast tumor prognostic characteristics and health-related quality of life. Although the results of numerous case-control and follow-up studies suggest that hormone replacement therapy modestly increases breast cancer risk, most studies have been unable to adjust adequately for frequency of mammographic screening. This is an important limitation because more frequent use of mammography screening among women who maintain hormone replacement prescriptions through regular physician visits may lead to increased detection of breast cancer relative to women who do not use hormone replacement therapy. Our study design, which involves an existing cohort identified through the New Hampshire Mammography Network (NHMN) - a statewide, population-based mammography registry comprising more than 150,000 women - overcomes this limitation. Using a baseline survey, administered at the time of mammography, we have already obtained breast cancer risk factor information, including current HRT use, from all women in the NHMN registry. Through NHMN we have already identified 74,200 women who are pre- or post-menopausal including approximately 26,700 current HRT users. We will follow these women for four years prospectively to ascertain new cases of breast cancer. All NHMN enrollees have already provided permission to link medical, radiologic and pathology data, and consented to further contact for research purposes. We will implement a supplemental survey in Years 1 and 4 to obtain a detailed history of HRT use, additional risk factor information and health-related quality of life. All other data will be obtained from the well established NHMN. Our primary specific aims are to evaluate the impact of HRT on 1) mammography performance (i.e., sensitivity and specificity of screening mammography, proportion of uninterpretable mammograms and consequent use of other imaging procedures); 2) breast cancer incidence (especially combination therapies); 3) breast cancer tumor prognostic characteristics (e.g., TNM stage, tumor grade, axillary lymph node status and estrogen receptor status). As more women consider use of HRT to prevent osteoporosis and other diseases, understanding its impact on quality of life is imperative. Therefore, a secondary aim is to assess the impact of HRT on health- related quality of life. Results of the proposed study will benefit radiologists who interpret mammograms, and women and their health care providers, who must balance the complex issues of disease risk and health-related quality of life when deciding whether or not to use hormone replacement therapy.